. The genetic language in prokaryotes. Evidences of an ancestral search for more efficient and accurate textual forms correlating with gene ancestry

LÓPEZ, J.L.; LOZANO, M.J.; PAGNUTTI A. L.; LAGARES, A.

Sede virtual

Congreso; XVI Congreso Argentino de Microbiología General (SAMIGE) y LVII Reunión de la SAIB; 2021

SAMIGE-SAIB

Languages are communication systems―either natural or formally created―aiming at the transmission of information between two physical/biological entities (i.e. languages are systems for the transfer of meaningful data). While the spoken communication among humans has been the best studied natural language, the genetic code-based transmission of information constitutes, by far, the most ancient and ubiquitous natural language which is also common (almost universal) and essential to all life forms and viruses. Such circumstance, and the early observation that cells do not make random use of codons with isoacceptor tRNAs, stimulated numerous investigations to understand the mutational and selective phenomena associated to the differential codon (“word”) choices in organisms with remarkable differences in their global genomic compositions (GC contents spanning from less than 20% to ca. 80%). In order to investigate the basis underlying specific codon preferences in the prokaryotic tree of life, we performed a comprehensive analysis of 29 different families including Bacteria and Archaea, and found 4 distinct behavioral groups (López et al., mBio 2020, doi.org/10.1128/mBio.00766-20). The analysis of core gene sets with increasing ancestries in each family lineage revealed that the codon usages became progressively more adapted to the tRNA pools. While, as previously reported, highly expressed genes presented the most optimized codon usage, the singletons contained always the less selectively favored codons. In agreement with previous reports, a C bias in 2- to 3-fold pyrimidine-ending codons, and a U bias in 4-fold codons occurred in all families, irrespective of the global genomic GC content. the U biases suggested that U3-mRNA–U34-tRNA interactions were responsible for a prominent codon optimization in both the most ancestral core and the highly expressed genes. A comparative analysis of sequences that encode conserved or variable translated products, with each one being under high and low expression levels, demonstrated that the efficiency was more relevant (by a factor of 2) than accuracy in modeling codon usage. Finally, by studying a model multipartite prokaryote genome a comprehensive analysis describing the inter- and intra-replicon heterogeneity of codon usages was performed (López et al., mBio 2019, doi.org/10.1128/mBio.00505-19.). Under the current view of the way cells make use of the 64 elements of their genetic code, novel parallels have to be elaborated to translate and contrast classical definitions from the cognitive language like redundancy, synonymy (do fully synonymous codons exist?), ambiguity/polysemy (such as that associated to UGA codons) and contextual effects, all referring to different instances of plurality. That exercise will help to understand the minimal biological needs that were required over evolution for the progressive emergence of specific semantic effects.